Is F9 p.Arg3Ser (c.7C>A) pathogenic?

F9 p.Arg3Ser (c.7C>A) is classified Likely benign in F9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-09). AlphaMissense: likely benign (0.1234); Very rare (popmax 0.00174%, afr); Associated with thrombophilia, X-linked, due to factor 9 defect.

What condition is associated with F9 p.Arg3Ser (c.7C>A)?

F9 p.Arg3Ser (c.7C>A) is associated with thrombophilia, X-linked, due to factor 9 defect, hemophilia B (ClinVar).

How common is F9 p.Arg3Ser (c.7C>A) in the general population?

F9 p.Arg3Ser (c.7C>A) is very rare (popmax 0.00174%, afr) (gnomAD).

What do computational predictors say about F9 p.Arg3Ser (c.7C>A)?

AlphaMissense predicts likely benign (score 0.1234) — an in-silico prediction, not a clinical call.

F9 p.Arg3Ser

c.7C>A · rs766259893 · VCV2929110

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1234 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00174%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

thrombophilia, X-linked, due to factor 9 defect

Computational evidence

Protein change
AlphaMissense	0.1234	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -6.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.69	GERP -2.5
Regional constraint	o/e 1.17	unconstrained · MANE · 6,280 bp · p 0.32 · regional, not allelic
Overall
CADD	1.196	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00174% African / African-American · 1/57,318 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000331% 4/1,207,811 alleles · very rare exomes 3/1,095,444 · genomes 1/112,367 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00174%	57,318
European (non-Finnish)	0.000336%	297,648

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: F9
Protein: p.Arg3Ser
Coding: c.7C>A
MANE Select: NM_000133
dbSNP: rs766259893
Type: single nucleotide variant
Location: chrX:139530771 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB

Full F9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

thrombophilia, X-linked, due to factor 9 defect — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hemophilia B

Similar variants

F9 p.Arg3Cys Benign ★★★ same residue
F9 p.Arg3His Benign ★★★ same residue
F9 p.Arg3= Likely benign ★ same residue
F9 c.520+13A>G Pathogenic ★★★ same condition
F9 c.88+1G>A Pathogenic ★★★ same condition
F9 c.88+5G>T Likely pathogenic ★★★ same condition
F9 p.Ala279Thr Pathogenic ★★★ ⚠ same condition
F9 p.Ala337Pro Likely pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/f9-p-arg3ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown